Project Summary The goal of this new Phase I Center of Biomedical Research Excellence (COBRE) proposal is to establish and develop a new interdisciplinary research Center within the University of Nevada, Reno (UNR), and the UNR School of Medicine (UNR Med) that is focused on fundamental molecular and cellular signal transduction mechanisms within the cardiovascular system. This COBRE will be unique, as there are no existing centers or institutes with a focus on basic cardiovascular research within the State of Nevada. The unifying scientific theme of the new COBRE is the discovery and characterization of novel molecular and cellular signaling mechanisms that regulate the cardiovascular system in health and disease. This research mission is significant, because cardiovascular diseases remain the leading causes of death and disability in the US and much of the world. We expect that COBRE-sponsored research programs will develop deep insight into the basic molecular and cellular signaling mechanisms that regulate cardiovascular function, thereby accelerating the rate of discovery of new treatments for common cardiovascular diseases and ultimately improving human health. The primary function of Phase I is to provide mentoring and support for COBRE?s Project Leaders, a group of four promising early-stage investigators, with the goal of developing them into fully established research scientists funded by independent Research Program Grants (RPGs), such as an NIH R01 or equivalent. The COBRE will also improve the research infrastructure at UNR and UNR Med by establishing and developing two new research cores?the Transgenic Animal Genotyping and Phenotyping Core (Core B) and the High Spatial and Temporal Resolution Imaging Core (Core C)?to serve the needs of the Project Leaders and the wider research community. Phase I of the COBRE will lay the groundwork for long-term sustainability of the Center by increasing the number of RPG-supported investigators within the thematic focus at UNR and UNR Med, and by promoting collaborations among these investigators to stimulate the development of new multi-PI R01s and Program Project Grants. Dr. Scott Earley, Professor of Pharmacology at UNR Med, is the Principal Investigator and COBRE Director. Dr. Earley is an accomplished investigator with an established track record of NIH R01 funding and publication in high-quality journals. Additional scientific leadership will be provided by a group of four outstanding established investigators with common interests in ion channels, localized Ca2+ signaling, intracellular signal transduction pathways, transgenic animal models, endothelial cell function, epigenetics, novel cell surface receptors, neuronal cardiovascular control, localized signaling domains, and excitation/contraction coupling in cardiomyocytes and smooth muscle cells. Successful completion of the objectives of Phase I will establish the Nevada COBRE in Molecular and Cellular Signal Transduction in the Cardiovascular System as a sustainable multidisciplinary research Center with a critical mass of investigators working within this thematic focus.